Comparative studies of the toxicity of standard reference materials in various cytotoxicity tests and in vivo implantation tests.

Polyurethane films that contained various amounts of zinc diethyldithiocarbamate (ZDEC) and zinc dibutyldithiocarbamate (ZDBC) were prepared as standard reference materials (SRM). Using three cell lines of V79, L929, and Balb/3T3 cells, the cytotoxicity of the dithiocarbamates and the SRM films were compared by agar diffusion assay, filter diffusion assay, neutral red assay, cell growth assay, and colony assay. Among these in vitro cytotoxicity tests, colony assay was found to be the most sensitive method for detecting the cytotoxicity. The cytotoxic potentials of extracts from SRM films correlated well with the concentrations of ZDEC or ZDBC involved in SRM. When various rubber materials including SRM and surgical rubber latex materials were tested, cytotoxic potentials of these extracts were also correlated with the inflammatory tissue capsule thickness in short-term implantation tests. On the basis of these results, the SRM is judged to be useful for validating test sensitivity, and comparing the correlation between in vitro and in vivo responses.